5-Iminodaunorubicin and N,N-dibenzyldaunorubicin are analogs of adriamycin that show improved properties. These compounds are being used as the points of departure in a systematic, multidisciplinary effort to develop still better analogs. Synthesis of new analogs is integrated with in vitro tests for DNA interaction, antitumor screening in mice, metabolism studies in tissues and whole animals, and determination of cardiotoxic effects. The cardiotoxic effects are determined by measuring electrocardiographic changes in treated rats, and by comparing effects on nucleolar ultrastructure of heart, liver, and muscle cells. A specific aspect of the metabolism studies is to compare the enhancement of microsomal O2 consumption after adding the various analogs; the resultant generation of oxygen radicals may be related to the biological action of the anthracyclines. Promising new analogs are 3'-deamino-3'-(4-morpholinyl)daunorubicin, which shows the greatest increase in potency of any adriamycin analogs so far, and 3'-deamino-3'-(4-methoxypiperidino)daunorubicin, which shows the greatest increase in efficacy, judging from results against mouse leukemia P388.